99 articles - From Friday Jul 01 2022 to Friday Jul 08 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Blood Adv |
International Consensus Statement on the Management of Cardiovascular Risk of Bruton's Tyrosine Kinase Inhibitors in CLL. Optimizing heart failure, arrhythmia, and hypertension control will likely improve tolerance and maintenance of BTKi therapy. However, additional studies are needed to identify the most optimal strategy for these drugs. |
| Thromb Haemost |
Assessment and Mitigation of Bleeding Risk in Atrial Fibrillation and Venous Thromboembolism: Executive Summary of a European and Asia-Pacific Expert Consensus Paper. Patient values and preferences, balancing the risk of bleeding against thromboembolism, are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice. |
meta-analyses and systematic reviews
| Blood Adv |
| Haematologica |
| Thromb Haemost |
Risk of Thromboembolic Events in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-analysis of Randomized Controlled Trials. There was no significant increase in the overall risk of VTE in patients treated with ICIs; however, special attention should be given to the risk of VTE in PD-1/PD-L1 inhibitor and CTLA-4 inhibitor combination therapy and PE in lung cancer patients. PD-L1 inhibitors were associated with a significant increase in ATE. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
BRD4 Degradation Blocks Expression of MYC and Multiple Forms of Stem Cell Resistance in Ph+ Chronic Myeloid Leukemia. Finally, dBET6 was found to suppress the in vitro survival of CML LSC and their engraftment in NSG mice. Together, targeting of BRD4 and MYC through BET degradation sensitizes CML cells against BCR::ABL1 TKI and is a potent approach to overcome multiple forms of drug resistance in CML LSC. |
| Ann Oncol |
Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial. Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2 mutated patients with PSROC compared to patients not previously receiving PARPi. The optimal strategy for patients who relapse after PARP inhibitors is an area of ongoing research. |
Therapeutic drug monitoring based precision dosing of oral targeted therapies in oncology: a prospective multicentre study. Pharmacokinetically guided dose optimization of oral targeted therapies was feasible in clinical practice and reduced the proportion of underexposed patients considerably. |
| Blood |
Abnormal Metaphase Cytogenetics Predicts Venous Thromboembolism in Myeloma: Derivation and Validation of the PRISM Score. Risk of VTE increased significantly with increasing score in both derivation and external validation datasets, with the sHR per 1-point increase being 1.28 (95% CI, 1.19-1.39; p<0.001) and 1.23 (95% CI, 1.07-1.41; p=0.004) respectively. While PRISM score can guide clinicians in identifying patients at a high risk of VTE, additional external validation is necessary for incorporation into routine clinical practice. |
Diagnosis and Management of AML in Adults: 2022 ELN Recommendations from an International Expert Panel. There have been major advances in our understanding of AML, including new knowledge about the molecular pathogenesis of AML, leading to an update of the disease classification, technological progress in genomic diagnostics and assessment of measurable residual disease, and the successful development of new therapeutic agents, such as FLT3, IDH1, IDH2, and BCL2 inhibitors. These advances have prompted this update which includes a revised ELN genetic risk classification, revised response criteria, and treatment recommendations. |
Early cardiac response is possible in stage IIIb cardiac AL amyloidosis and is associated with prolonged survival. A baseline difference of involved/uninvolved free light chains (dFLC) >50 mg/L (OR 0.21, P=0.024) and a bone marrow plasma cell infiltrate >10% (OR 0.23, P=0.040) were negative predictors of 90-day cardiac response. Early cardiac responses are rare but possible in stage IIIb AL amyloidosis and translate in longer survival. |
Genetic testing in severe aplastic anemia is required for optimal hematopoietic cell transplant outcomes. Genetic testing should be part of the diagnostic evaluation for al patients with SAA to tailor therapeutic regimens. Carriers of a pathogenic variant in an IBMFS gene can follow HCT regimens for acquired SAA. |
How I Treat and Prevent COVID-19 in Patients with Hematologic Malignancies and Recipients of Cellular Therapies. Selection and administration of the best treatment options are based on host factors; virus factors, including circulating SARS-CoV-2 variants; and therapeutic considerations, including the clinical efficacy, availability, and practicality of treatment and its associated side effects, including drug-drug interactions. In this paper, we discuss how we approach managing COVID-19 in patients with hematologic malignancies and recipients of HCT and cell therapy. |
Human complete NFAT1 deficiency causes a triad of joint contractures, osteochondromas, and B cell malignancy. Systematic single-cell-omic analyses in peripheral blood mononuclear cells (PBMCs) revealed an environment that promotes lymphomagenesis with accumulation of naïve B cells (enriched for oncogenic signatures - MYC, JAK1), exhausted CD4+ T cells, impaired T follicular helper cells, and aberrant CD8+ T cells. This work highlights the pleiotropic role of human NFAT1, will empower the diagnosis of additional patients with NFAT1 deficiency, and further define the detrimental effects associated with long-term use of calcineurin inhibitors. |
Ibrutinib improves survival compared to chemotherapy in mantle cell lymphoma with central nervous system relapse. The addition of intrathecal chemotherapy to systemic CNS directed therapy was not associated with superior OS (p=0.502), as the morphological variant (classical versus others, p=0.118). Ibrutinib was associated with superior survival compared to BBB penetrating chemotherapy in patients with CNS relapse of MCL, and should be considered as a therapeutic option. |
Immune Complications and their Management in Inherited and Acquired Bleeding Disorders. ITI serves as an important proof-of-principle that antigen-specific immune tolerance can be achieved in humans through repeated antigen administration, even in the absence of immune suppression. Finally, novel immunotherapy approaches that are still in pre-clinical phase such as cellular (for instance regulatory T cell) immunotherapies, gene therapy, and oral antigen administration are discussed. |
KIR-Favorable TCR-aß/CD19-Depleted Haploidentical HCT in Children with ALL/AML/MDS: Primary Analysis of PTCTC ONC1401. This prospective, multicenter study showed improved outcomes using TCR-aß/CD19-depleted haploidentical donors using RTC for children with acute leukemia and MDS; randomized trials comparing this approach with matched unrelated donors are warranted (ClinicalTrials. gov NCT02646839). |
Lymph node excisions provide more precise lymphoma diagnoses than core biopsies: a French Lymphopath network survey. Overall, although CNB accurately diagnoses lymphoma in most instances, it increases the risk of erroneous or non-definitive conclusions. This large-scale survey also emphasizes the need for systematic expert review in cases of lymphoma suspicion, especially in those sampled by CNB. |
Oligoclonal T-cell expansion in a patient with bone marrow failure after CD19 CAR-T for Richter transformed DLBCL. Gene expression profiling revealed upregulation of exhaustion markers on (CAR) T-cells and decreased expression of genes involved in STAT signalling and inflammatory response. In conclusion, this case highlights the complex nature of CAR-T-related hematological toxicity and introduces oligoclonal (CAR) T-cell expansion as a potential contributing pathophysiologic mechanism. |
Physioxia induced Downregulation of Tet2 in Hematopoietic Stem Cells contributes to Enhanced Self-renewal. The lack of response to changes in oxygen tension in Tet2-/- HSCs was associated with similar changes in self-renewal and quiescence genes among WT-HSC-physioxia, Tet2-/-HSC-physioxia and Tet2-/-HSC-air. We define a novel molecular program involving Tet2 in regulating HSCs under physioxia. |
Race, Rituximab, and Relapse in TTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression following rituximab treatment. How race, racism, and the social determinants of health contribute to the disparity in relapse risk in iTTP deserve further study. |
Structures of VWF tubules before and after concatemerization reveal a mechanism of disulfide bond exchange. In addition, the structures reveal disulfide states prior to and after disulfide bond-mediated concatemerization. The structures and proposed assembly mechanism provide a foundation to rationalize VW disease-causing mutations. |
Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis. Gly40Ala) rescued UBA1b levels to those of canonical mutations. We conclude that regulation of residual UBA1b translation is fundamental to the pathogenesis of VEXAS syndrome and contributes to disease prognosis. |
| Blood Adv |
BMX Kinase Mediates Gilteritinib Resistance in FLT3-mutated AML through Microenvironmental Factors. Subsequent gene module analyses indicated that gilteritinib responsiveness was associated with lymphocyte differentiation and myeloid leukocyte activation, whereas unresponsiveness to gilteritinib was associated with upregulation of cell-cycle, DNA/RNA metabolic processes, and protein translation. Collectively, these findings indicate a crucial role for microenvironment-mediated factors modulated by BMX in the escape from targeted therapy and have implications for the development of novel therapeutic interventions to restore sensitivity to gilteritinib. |
Clinical Characteristics and Outcomes of IgD Myeloma: Experience across UK National Trials. Survival outcomes for IgD myeloma have significantly improved and are now comparable to other myeloma types due to earlier diagnosis, novel therapies and improved supportive care. (Myeloma IX International Standard Randomised Controlled Trial Number: 68454111, Myeloma XI International Standard Randomised Controlled Trial Number: 49407852). |
Efficacy and safety of azathioprine during remission of immune-mediated thrombotic thrombocytopenic purpura. At least one adverse event (AE) occurred in 30% of the patients, usually gastrointestinal toxicity, prompting treatment interruption in 14% of treated patients. Thus, azathioprine proved to be effective in terms of clinical relapse prevention, attainment of a durable ADAMTS13 remission, with infrequent and relatively mild AEs. |
Evaluating the impact of eligibility criteria in first-line clinical trials for follicular lymphoma: a MER/LEO cohort analysis. These data suggest that management of older individuals with FL may not be fully informed by recent clinical trials. Moreover, liberalizing stage and platelet criteria might expand the eligible population and allow for quicker trial accrual without impacting outcomes. |
GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12. Finally, we show that GRK2 binds to endogenous Gß |
High early death rates, treatment resistance, and short survival of Black adolescents and young adults with AML. Reduced response rates to induction chemotherapy and leukemic clone persistence suggest a need for different treatment intensities and/or modalities in Black AYA patients with AML. Higher early death rates suggest a delay in diagnosis and treatment, calling for systematic changes to patient care. |
HMGA2 expression defines a subset of AML with immature transcriptional signature and vulnerability to G2/M inhibition. Accordingly, small molecules that target G2/M proteins were preferentially active in vitro and in vivo on HMGA2+ AML specimens. Together, our findings suggest that HMGA2 is a key functional determinant in AML and is associated with stem cell features, G2/M status and related drug sensitivity. |
ICOS ImmunoPET Enables Visualization of Activated T Cells and Early Diagnosis of Murine Acute Gastrointestinal GvHD. Importantly, we demonstrate that the 89Zr-DFO-ICOS mAb PET tracer does not affect GvHD pathogenesis or the graft-versus-tumor (GvT) effect of the transplant procedure. Our data identify ICOS immunoPET as a promising strategy for early GvHD diagnosis prior to the appearance of clinical symptoms. |
Improved GRFS after posttransplant cyclophosphamide-based vs ATG-based HLA-mismatched unrelated donor transplant. One-year non-relapse mortality was greater after ATG-based prophylaxis: (38%, 23% - 52%; versus 16%, 9% - 25%; P < 0.001). In summary, PTCy based prophylaxis resulted in superior GRFS and OS in recipients of MMUD. |
In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies. For instance, we identified Fermt3, a master regulator of integrin signaling, as an in vivo-specific dependency with high prognostic relevance. Overall, we demonstrate an experimental and computational pipeline for genome-wide functional screens in vivo in AML and provide a genome-wide resource of essential drivers of leukemic growth in vivo. |
Platelet activation and partial desensitization are associated with viral xenophagy in patients with severe COVID-19. They had large LC3-positive structures and increased levels of LC3II with a co-localization of LC3 and Spike, suggesting that platelets can digest SARS-CoV-2 material by xenophagy in critically ill patients. Altogether, these data show that during severe COVID-19, platelets get activated, become partly desensitized, and develop a selective autophagy response. |
Reduced-dose WBRT as consolidation treatment for patients with primary CNS lymphoma: a LOC-network study. The results of the 36-month neuropsychological follow-up for a subset of patients appeared quite reassuring, with most patients exhibiting maintenance of or improvements in their baseline conditions. Our results, combined with phase II study results, support the use of rdWBRT instead of sdWBRT as a consolidation treatment option in <60-year-old patients showing CR after induction treatment. |
Safety and feasibility of stem cell boost as a salvage therapy for severe hematotoxicity after CD19 CAR T-cell therapy. These data indicate that the transplantation of available stem cell products for post-CAR-T cytopenias is clinically feasible, safe and efficacious. Further studies are needed to assess, whether a pre-emptive collection of stem cells can be justified in selected high-risk patients. |
Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Siltuximab treatment prolongs PFS, rapidly improves symptomatology, and provides meaningful clinical benefit despite some laboratory tests and enlarged lymph nodes taking months to normalize in treatment responders. These data support the continued front-line use of siltuximab for iMCD, as recommended by international guidelines. |
| Blood Cancer J |
B cell receptor signaling drives APOBEC3 expression via direct enhancer regulation in chronic lymphocytic leukemia B cells. We also find that enhancer-regulated APOBEC3 expression contributes to replication stress in malignant B cells. In total we demonstrate a novel mechanism for BTKi suppression of APOBEC3 expression via direct enhancer regulation in an NFATc1-dependent manner, implicating BCR signaling as a potential regulator of leukemic genomic instability. |
| Haematologica |
| J Hematol Oncol |
Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. |
| Lancet Haematol |
[18F]FDG-PET-CT compared with CT for persistent or recurrent neutropenic fever in high-risk patients (PIPPIN): a multicentre, open-label, phase 3, randomised, controlled trial. [ 18 F]FDG-PET-CT can support decision making regarding antimicrobial cessation or de-escalation and should be considered in the management of patients with haematological diseases and persistent or recurrent high-risk neutropenic fever after chemotherapy or transplant conditioning. Funding National Health and Medical Research Council Centre of Research Excellence (APP1116876), Melbourne Health foundation, Gilead Research Fellowship grants supported this study. |
Associations between non-anaemic iron deficiency and outcomes following elective cardiac surgery (IDOCS): a prospective cohort study. Routine preoperative investigation for iron deficiency in patients without anaemia undergoing elective cardiac surgery using the definitions we tested might be low-value care. Funding Australian and New Zealand College of Anaesthetists Foundation. |
Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Futility of the treatment under the initial study design assumptions could not be conclusively assessed owing to under-representation of older patients and consequent low event rates. Funding SNSF (National Research Programme COVID-19 NRP78: 198352), University Hospital Zurich, University of Zurich, Dr-Ing Georg Pollert (Berlin), Johanna Dürmüller-Bol Foundation. |
SHR2554, an EZH2 inhibitor, in relapsed or refractory mature lymphoid neoplasms: a first-in-human, dose-escalation, dose-expansion, and clinical expansion phase 1 trial. Funding Jiangsu Hengrui Pharmaceuticals. Translation For the Chinese translation of the abstract see Supplementary Materials section. |
Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): an open-label, multicentre, randomised, controlled, phase 3b trial. Although the trial was terminated early, our data, combined with data from similar studies, provide further insights to inform international guidelines and influence clinical practice. Funding The Thrombosis Research Institute and Sanofi UK. |
| Leukemia |
Combinatorial genetics reveals the Dock1-Rac2 axis as a potential target for the treatment of NPM1;Cohesin mutated AML. Importantly, the Dock1/Rac pathway is targetable in Npm1 cA/+ ; Smc3 |
Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: -72.8, -47.9; p |
| Thromb Haemost |
Performance of a Qualitative Point-of-Care Strip Test to Detect DOAC Exposure at the Emergency Department: A Cohort-Type Cross-Sectional Diagnostic Accuracy Study. The DOAC Dipstick sensitively identified effective thrombin and factor Xa inhibition in a real-world cohort of patients presenting at an emergency department. Therefore, the dipstick might provide a valuable test to detect relevant DOAC exposure in emergencies, although further studies will be needed to confirm these findings. |
Resumption of Antiplatelet Therapy after Major Bleeding. Shared decision-making involving various disciplines is essential to determine the optimal strategy. The present article addresses clinically relevant questions focusing on the most life-threatening or frequently occurring bleeding events, such as intracranial hemorrhage and gastrointestinal bleeding, and discusses the evidence for antiplatelet therapy resumption using individual risk assessment in high-risk cardiovascular disease patients. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
Immunotherapy in unresectable stage III non-small cell lung cancer: state of the art and novel therapeutic approaches. radiomics and ctDNA). Identifying distinct subsets of patients to tailor anti-cancer treatment is a priority, especially in a heterogeneous disease such as stage III NSCLC. |
| Blood |
| J Hematol Oncol |
Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m 6 A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m 6 A methylation research. |
Recent progress on vascular endothelial growth factor receptor inhibitors with dual targeting capabilities for tumor therapy. Given the synergistic effect of VEGFR and other therapies in tumor development and progression, VEGFR dual-target inhibitors are becoming an attractive approach due to their favorable pharmacodynamics, low toxicity, and anti-resistant effects. This perspective provides an overview of the development of VEGFR dual-target inhibitors from multiple aspects, including rational target combinations, drug discovery strategies, structure-activity relationships and future directions. |
Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors. We also evaluate the significance of the STIE, TIME, and their interactions as well as changes after local radiotherapy and systemic immunotherapy or combined immunotherapy. We focus our review on the evidence of lung cancer, hepatocellular carcinoma, and nasopharyngeal carcinoma, aiming to reshape STIE and TIME to enhance immunotherapy efficacy. |
| Lancet Haematol |
Choosing between intensive and less intensive front-line treatment approaches for older patients with newly diagnosed acute myeloid leukaemia. In this Viewpoint, we review the retrospective and prospective data supporting both intensive chemotherapy and low-intensity venetoclax-based approaches in older patients with acute myeloid leukaemia. We also discuss our own approach to the management of older or unfit patients with acute myeloid leukaemia, including how cytomolecular features have a role in establishing the optimal front-line therapy. |
Myelodysplastic syndrome and autoimmune disorders: two sides of the same coin? We note that systemic inflammatory and autoimmune diseases are often steroid-dependent; however, studies have also evaluated the roles of other immunomodulating therapies. In this Viewpoint, we critically appraise and review the literature on the epidemiology, pathophysiology, and management of systemic inflammatory and autoimmune diseases that are associated with myelodysplastic syndromes and related diseases. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| J Hematol Oncol |
First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML. |
| Lancet Haematol |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| CA Cancer J Clin |
| Haematologica |
| Lancet Haematol |
| Leukemia |